Dimethylformamide → methyl 5-(1-(2-cyano-1-cyclopropylethyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate

HRID 1853051Notes

Reaction equation

HRID 1853051 reaction equation
Cl.[NH:2]1[CH:6]=[C:5]([C:7]2[N:12]3[CH:13]=[CH:14][N:15]=[C:11]3[CH:10]=[C:9]([C:16]([O:18][CH3:19])=[O:17])[N:8]=2)[CH:4]=[N:3]1.[CH:20]1([CH:23]=[CH:24][C:25]#[N:26])[CH2:22][CH2:21]1.CN(C=O)C.C1CCN2C(=NCCC2)CC1>CCOC(C)=O>[C:25]([CH2:24][CH:23]([N:2]1[CH:6]=[C:5]([C:7]2[N:12]3[CH:13]=[CH:14][N:15]=[C:11]3[CH:10]=[C:9]([C:16]([O:18][CH3:19])=[O:17])[N:8]=2)[CH:4]=[N:3]1)[CH:20]1[CH2:22][CH2:21]1)#[N:26]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 670567823-CyclopropylacrylonitrileHCID 86685326methyl 5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate hydrochloride

Product 1

HCID 67456699methyl 5-(1-(2-cyano-1-cyclopropylethyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylateYield 35.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 100 mL flask, methyl 5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate hydrochloride (0.300 g, 1.07 mmol) and 3-cyclopropylacrylonitrile (Preparation B; 0.300 g, 3.22 mmol) were suspended in DMF (5.36 mL, 1.07 mmol) and DBU (0.722 mL, 4.83 mmol) added in one portion. The reaction mixture was stirred at ambient temperature for 15 hours. The reaction mixture was diluted in EtOAc and washed with water and brine. The combined organic layers were dried over MgSO4, filtered, and concentrated down to a yellow oil. Purification of the crude material by silica chromatography using a gradient of 50-100% EtOAc afforded methyl 5-(1-(2-cyano-1-cyclopropylethyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate (0.127 g, 0.378 mmol, 35.2% yield) as a yellow oil. MS (apci) m/z=337.2 (M+H).

Workup

  1. washwashed with water and brine
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated down to a yellow oil
  5. customPurification of the crude material by silica chromatography

Sources & evidence

ORD record
ord-e59a4f1628a04ba2a0d5554684cf527b
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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